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1.
Front Public Health ; 12: 1378723, 2024.
Article En | MEDLINE | ID: mdl-38706551

Background: Strengthening the construction of community resilience and reducing disaster impacts are on the agenda of the Chinese government. The COVID-19 pandemic could alter the existing community resilience. This study aims to explore the dynamic change trends of community resilience in China and analyze the primary influencing factors of community resilience in the context of COVID-19, as well as construct Community Resilience Governance System Framework in China. Methods: A community advancing resilience toolkit (CART) was used to conduct surveys in Guangdong, Sichuan, and Heilongjiang provinces in China in 2015 and 2022, with community resilience data and information on disaster risk awareness and disaster risk reduction behaviors of residents collected. The qualitative (in-depth interview) data from staffs of government agencies and communities (n = 15) were pooled to explore Community Resilience Governance System Framework in China. Descriptive statistics analysis and t-tests were used to investigate the dynamic development of community resilience in China. Hierarchical regression analysis was performed to explore the main influencing factors of residential community resilience with such socio-demographic characteristics as gender and age being controlled. Results: The results indicate that community resilience in China has improved significantly, presenting differences with statistical significance (p < 0.05). In 2015, connection and caring achieved the highest score, while disaster management achieved the highest score in 2022, with resources and transformative potential ranking the lowest in their scores in both years. Generally, residents presented a high awareness of disaster risks. However, only a small proportion of residents that were surveyed had participated in any "community-organized epidemic prevention and control voluntary services" (34.9%). Analysis shows that core influencing factors of community resilience include: High sensitivity towards major epidemic-related information, particular attention to various kinds of epidemic prevention and control warning messages, participation in epidemic prevention and control voluntary services, and formulation of epidemic response plans. In this study, we have constructed Community Resilience Governance System Framework in China, which included community resilience risk awareness, community resilience governance bodies, community resilience mechanisms and systems. Conclusion: During the pandemic, community resilience in China underwent significant changes. However, community capital was, is, and will be a weak link to community resilience. It is suggested that multi-stages assessments of dynamic change trends of community resilience should be further performed to analyze acting points and core influencing factors of community resilience establishment at different stages.


COVID-19 , Resilience, Psychological , Humans , China/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Male , Female , Surveys and Questionnaires , Adult , Middle Aged , SARS-CoV-2 , Pandemics
3.
Ann Surg ; 279(4): 588-597, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38456278

OBJECTIVE: To compare the effect of low and standard pneumoperitoneal pressure (PP) on the occurrence of gas embolism during laparoscopic liver resection (LLR). BACKGROUND: LLR has an increased risk of gas embolism. Although animal studies have shown that low PP reduces the occurrence of gas embolism, clinical evidence is lacking. METHODS: This parallel, dual-arm, double-blind, randomized controlled trial included 141 patients undergoing elective LLR. Patients were randomized into standard ("S," 15 mm Hg; n = 70) or low ("L," 10 mm Hg; n = 71) PP groups. Severe gas embolism (≥ grade 3, based on the Schmandra microbubble method) was detected using transesophageal echocardiography and recorded as the primary outcome. Intraoperative vital signs and postoperative recovery profiles were also evaluated. RESULTS: Fewer severe gas embolism cases (n = 29, 40.8% vs n = 47, 67.1%, P = 0.003), fewer abrupt decreases in end-tidal carbon dioxide partial pressure, shorter severe gas embolism duration, less peripheral oxygen saturation reduction, and fewer increases in heart rate and lactate during gas embolization episodes was found in group L than in group S. Moreover, a higher arterial partial pressure of oxygen and peripheral oxygen saturation were observed, and fewer fluids and vasoactive drugs were administered in group L than in group S. In both groups, the distensibility index of the inferior vena cava negatively correlated with central venous pressure throughout LLR, and a comparable quality of recovery was observed. CONCLUSIONS: Low PP reduced the incidence and duration of severe gas embolism and achieved steadier hemodynamics and vital signs during LLR. Therefore, a low PP strategy can be considered a valuable choice for the future LLR.


Embolism, Air , Laparoscopy , Animals , Humans , Carbon Dioxide/adverse effects , Embolism, Air/etiology , Embolism, Air/prevention & control , Embolism, Air/diagnosis , Laparoscopy/adverse effects , Laparoscopy/methods , Liver/surgery , Pneumoperitoneum, Artificial/adverse effects
4.
J Hazard Mater ; 469: 134064, 2024 May 05.
Article En | MEDLINE | ID: mdl-38513444

Water vapor from respiration can severely accelerate the charge dissipation of the face mask, reducing filtration efficiency. Moreover, the foul odor from prolonged mask wear tends to make people remove their masks, leading to the risk of infection. In this study, an electro-blown spinning electroactive nanofibrous membrane (Zn/CB@PAN) with antibacterial and deodorization properties was prepared by adding zinc (Zn) and carbon black (CB) nanoparticles to the polyacrylonitrile (PAN) nanofibers, respectively. The filtration efficiency of Zn/CB@PAN for PM0.3 was > 99% and could still maintain excellent durability within 4 h in a high-humidity environment (25 â„ƒ and RH = 95%). Moreover, the bacterial interception rate of the Zn/CB@PAN could reach 99.99%, and it can kill intercepted bacteria. In addition, the deodorization rate of Zn/CB@PAN in the moist state for acetic acid was 93.75% and ammonia was 95.23%, respectively. The excellent filtering, antibacterial, and deodorizing performance of Zn/CB@PAN can be attributed to the synergistic effect of breath-induced Zn/CB galvanic couples' electroactivity, released metal ions, and generated reactive oxygen species. The developed Zn/CB@PAN could capture and kill airborne environmental pathogens under humid environments and deodorize odors from prolonged wear, holding promise for broad applications as personal protective masks.


Nanofibers , Humans , Anti-Bacterial Agents , Acetic Acid , Zinc , Ammonia , Filtration
5.
Dig Dis Sci ; 69(4): 1214-1227, 2024 Apr.
Article En | MEDLINE | ID: mdl-38376789

BACKGROUND: HSK3486 (ciprofol), a new candidate drug similar to propofol, exerts sedative and hypnotic effects through gamma-aminobutyric acid type A receptors; however, its potential role in colorectal cancer is currently unknown. AIMS: This study aimed to evaluate the effects of HSK3486 on colorectal cancer cell proliferation. METHODS: Imaging was performed to detect reactive oxygen species and mitochondrial membrane potential. Western blotting was used to determine the expression of target signals. The HSK3486 molecular mechanism was investigated through ATPase inhibitory factor 1 knockdown and xenograft model experiments to assess mitochondrial function in colorectal cancer cells. RESULTS: Cell Counting Kit-8 and Annexin V/propidium iodide double staining assays showed that HSK3486 inhibited colorectal cancer cell proliferation in a concentration-dependent manner. In addition, HSK3486 treatment increased the expression of B-cell lymphoma-2-associated X, cleaved caspase 3, and cleaved poly (ADP-ribose) polymerase, whereas myeloid cell leukemia-1 and B-cell lymphoma 2 expression decreased. HSK3486 promoted mitochondrial dysfunction by inducing ATPase inhibitor factor 1 expression. Furthermore, HSK3486 promoted oxidative stress, as shown by the increase in reactive oxygen species and lactate dehydrogenase levels, along with a decrease in mitochondrial membrane potential and ATP levels. ATPase inhibitor factor 1 small interfering RNA pretreatment dramatically increased the mitochondrial membrane potential and tumor size in a xenograft model following exposure to HSK3486. CONCLUSION: Collectively, our findings revealed that HSK3486 induces oxidative stress, resulting in colorectal cancer cell apoptosis, making it a potential candidate therapeutic strategy for colorectal cancer.


Apoptosis , Colorectal Neoplasms , Humans , Adenosine Triphosphatases/metabolism , Adenosine Triphosphatases/pharmacology , Adenosine Triphosphatases/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Membrane Potential, Mitochondrial , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , ATPase Inhibitory Protein/drug effects
6.
Eur Radiol ; 2024 Jan 04.
Article En | MEDLINE | ID: mdl-38172442

OBJECTIVES: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. METHODS: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan-Meier survival and Cox regression. RESULTS: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.08-3.76, p = 0.028), hyperhomocysteinaemia (HHcy) (OR 5.08, 95% CI 2.34-11.05, p < 0.001), and smoking history (OR 3.49, 95% CI 1.08-11.31, p = 0.037). During the follow-up of 63.9 ± 13.2 months (median 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and the RNF213 p.R4810K variant were risk factors for stroke. CONCLUSION: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE. CLINICAL RELEVANCE STATEMENT: Vessel wall enhancement in moyamoya disease is closely associated with poor prognosis, especially related to the ring finger protein 213 p.R4810K variant, hyperhomocysteinaemia, and smoking, providing crucial risk assessment information for the clinic. KEY POINTS: • The baseline presence of vessel wall enhancement is significantly associated with poor prognosis in moyamoya disease. • The ring finger protein 213 p.R4810K variant is strongly associated with vessel wall enhancement and poor prognosis in moyamoya disease. • Hyperhomocysteinaemia and smoking are independent risk factors for vessel wall enhancement in moyamoya disease.

7.
BMC Ophthalmol ; 23(1): 489, 2023 Nov 29.
Article En | MEDLINE | ID: mdl-38030997

BACKGROUND: Familial exudative vitreoretinopathy (FEVR) is a genetic eye disorder that leads to abnormal development of retinal blood vessels, resulting in vision impairment. This study aims to identify pathogenic variants by targeted exome sequencing in 9 independent pedigrees with FEVR and characterize the novel pathogenic variants by molecular dynamics simulation. METHODS: Clinical data were collected from 9 families with FEVR. The causative genes were screened by targeted next-generation sequencing (TGS) and verified by Sanger sequencing. In silico analyses (SIFT, Polyphen2, Revel, MutationTaster, and GERP + +) were carried out to evaluate the pathogenicity of the variants. Molecular dynamics was simulated to predict protein conformation and flexibility transformation alterations on pathogenesis. Furthermore, molecular docking techniques were employed to explore the interactions and binding properties between LRP5 and DKK1 proteins relevant to the disease. RESULTS: A 44% overall detection rate was achieved with four variants including c.4289delC: p.Pro1431Argfs*8, c.2073G > T: p.Trp691Cys, c.1801G > A: p.Gly601Arg in LRP5 and c.633 T > A: p.Tyr211* in TSPAN12 in 4 unrelated probands. Based on in silico analysis and ACMG standard, two of them, c.4289delC: p.Pro1431Argfs*8 and c.2073G > T: p.Trp691Cys of LRP5 were identified as novel pathogenic variants. Based on computational predictions using molecular dynamics simulations and molecular docking, there are indications that these two variants might lead to alterations in the secondary structure and spatial conformation of the protein, potentially impacting its rigidity and flexibility. Furthermore, these pathogenic variants are speculated to potentially influence hydrogen bonding interactions and could result in an increased binding affinity with the DKK1 protein. CONCLUSIONS: Two novel genetic variants of the LRP5 gene were identified, expanding the range of mutations associated with FEVR. Through molecular dynamics simulations and molecular docking, the potential impact of these variants on protein structure and their interactions with the DKK1 protein has been explored. These findings provide further support for the involvement of these variants in the pathogenesis of the disease.


Eye Diseases, Hereditary , Retinal Diseases , Humans , Familial Exudative Vitreoretinopathies , Retinal Diseases/genetics , Retinal Diseases/metabolism , Molecular Docking Simulation , Eye Diseases, Hereditary/genetics , Tetraspanins/genetics , DNA Mutational Analysis , Mutation , Pedigree , Phenotype , Low Density Lipoprotein Receptor-Related Protein-5/genetics , Low Density Lipoprotein Receptor-Related Protein-5/metabolism
8.
Front Neurol ; 14: 1243453, 2023.
Article En | MEDLINE | ID: mdl-37915379

Background: Despite continuous advances in microsurgical and endovascular techniques, the treatment of complex aneurysms remains challenging. Aneurysms that are dilemmatic for conventional clipping or endovascular coiling often require bypass as part of a strategy to reduce the risk of ischemic complications. In anatomically favorable sites, the intracranial-intracranial in situ bypass may be an appealing choice. This article details the surgical strategies, operative nuances, and clinical outcomes of this technique with a consecutive series in our department. Methods: A retrospective review of a prospectively maintained neurosurgical patient database was performed to identify all patients treated with side-to-side in situ bypass from January 2016 to June 2022. In total, 12 consecutive patients, including 12 aneurysms, were identified and included in the series. The medical records, surgical videos, neuroimaging studies, and follow-up clinic notes were reviewed for every patient. Results: Of the 12 aneurysms, there were 5 middle cerebral artery aneurysms, 4 anterior cerebral artery aneurysms, and 3 posterior inferior cerebellar artery aneurysms. The morphology of the aneurysms was fusiform in 8 patients and saccular in the remaining 4 patients. There were 3 patients presented with subarachnoid hemorrhage. The treatment modality was simple in situ bypass in 8 cases and in situ bypass combined with other modalities in 4 cases. Bypass patency was confirmed in all cases by intraoperative micro-doppler probe and (or) infrared indocyanine green (ICG) video angiography intraoperatively and with digital subtraction angiography (DSA) or computed tomography angiography (CTA) postoperatively. None of the patients developed a clinically manifested stroke due to the procedure though a callosomarginal artery was intentionally removed in one patient. The median follow-up period was 16.2 months (6-36). All patients had achieved improved or unchanged modified Rankin scale scores at the final follow-ups. Conclusion: Cerebral revascularization technique remains an essential skill for the treatment of complex aneurysms. The in situ bypass is one of the most effective techniques to revascularize efferent territory when vital artery sacrifice or occlusion is unavoidable. The configuration of in situ bypass should be carefully tailored to each case, with consideration of variations in anatomy and pathology of the complex aneurysms.

9.
Cell Biochem Funct ; 41(5): 553-563, 2023 Jul.
Article En | MEDLINE | ID: mdl-37218093

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and the etiology is unknown. Metabolic dysfunction is present in patients with ASD. In the current study, untargeted metabolomics was employed to screen the differential metabolites in the liver of BTBR mouse model of autism, and MetaboAnalyst 4.0 was used for metabolic pathway analysis. Mice were killed, and liver samples were collected for untargeted metabolomics analysis and examination of histopathology. Finally, 12 differential metabolites were identified. The intensities of phenylethylamine, 4-Guanidinobutanoic acid, leukotrieneD4, and SM(d18:1/24:1(15Z)) were significantly upregulated (p < .01), and the intensities of estradiol, CMP-N-glycoloylneuraminate, retinoyl ß-glucuronide,4-phosphopantothenoylcysteine, aldophosphamide, taurochenodesoxycholic acid, taurocholic acid, and dephospho-CoA were significantly downregulated (p < .01) in the BTBR group compared with C57 control group, indicating that differences between BTBR and C57 groups were observed in metabolic patterns. Disturbed pathways of the BTBR mice involved lipid metabolism, retinol metabolism, and amino acid and energy metabolism, revealing that bile acid-mediated activation of LXRα might contribute to metabolic dysfunction of lipid and leukotriene D4 produced by the activation of 5-LOX led to hepatic inflammation. Pathological changes in the liver tissue, such as hepatocyte vacuolization, and small amounts of inflammatory and cell necrosis, further supported metabolomic results. Moreover, Spearman's rank correlation revealed that there is a strong relationship between metabolites across liver and cortex, suggesting liver may exert action by connecting peripheral and neural systems. These findings were likely to be of pathological importance or a cause/consequence of autism, and may provide insight into key metabolic dysfunction to target potential therapeutic strategies relating to ASD.


Autism Spectrum Disorder , Autistic Disorder , Mice , Animals , Autistic Disorder/metabolism , Autistic Disorder/pathology , Autism Spectrum Disorder/metabolism , Mice, Inbred Strains , Liver/metabolism , Metabolomics , Disease Models, Animal , Mice, Inbred C57BL
10.
Chem Commun (Camb) ; 59(33): 4962-4965, 2023 Apr 20.
Article En | MEDLINE | ID: mdl-37014714

The small molecule 5,15-di(thiophen-2-yl) porphyrin (TP) was developed for new dual-ion symmetric organic batteries (DSOBs). It delivered a capacity of 150 mA h g-1 at 0.2 A g-1 with a high voltage of 2.7 V, and up to 1500 cycles were achieved. This work offers a new approach for developing high-performance dual-ion organic symmetric batteries.

11.
Front Genet ; 14: 1145426, 2023.
Article En | MEDLINE | ID: mdl-36999054

Purpose: To screen VSX1 gene sequence variations and describe the clinical features of families with keratoconus (KC) from northwest China. Methods: We screened VSX1 sequence variations and clinical data of 37 families including 37 probands with diagnosed KC from Ningxia Eye Hospital (China). VSX1 was screened by targeted next-generation sequencing (NGS) and verified by Sanger sequencing. In silico analysis including Mutation Taster, MutationAssessor, PROVEAN, MetaLR, FATHMM, M-CAP, FATHMM-XF_coding and DANN was performed to identify the pathogenicity of the sequence variations as well as the conserved amino acid variations of VSX1 was implemented by Clustal X. All subjects were assessed in Pentacam Scheimpflug tomography and corneal biomechanical Corvis ST examinations. Results: Five VSX1 gene variants, were identified in six (16.2%) unrelated families with KC. In silico analysis predicted deleterious effects of the three missense variants (p.G342E, p.G160V, and p.L17V) in the encoded protein. Another previously reported synonymous variation (p.R27R) in the first exon and one heterozygous change in the first intron (c.425-73C>T) were identified in three KC families. Clinical examination of the asymptomatic first-degree parents from these six families who shared the gene with the proband had suspected KC changes in topographic and biomechanical markers. These variants co-segregated with the disease phenotype in all affected individuals but not in unaffected family members or healthy controls, though with variable expressivity. Conclusion: The variant p.G342E of VSX1 is implicated in the pathogenesis of KC, which expands the range of the spectrum of VSX1 mutations with an autosomal dominant inheritance pattern and variable expression in the clinical phenotype. Genetic screening combined with clinical phenotype may help in the genetic counseling of patients with KC and identification of individuals with subclinical KC.

12.
J Mol Neurosci ; 73(1): 15-27, 2023 Jan.
Article En | MEDLINE | ID: mdl-36574152

The etiology and pathology of autism spectrum disorders (ASDs) are still poorly understood, which largely limit the treatment and diagnosis of ASDs. Emerging evidence supports that abnormal metabolites in the cerebral cortex of a BTBR mouse model of autism are involved in the pathogenesis of autism. However, systematic study on global metabolites in the cerebral cortex of BTBR mice has not been conducted. The current study aims to characterize metabolic changes in the cerebral cortex of BTBR mice by using an untargeted metabolomic approach based on UPLC-Q-TOF/MS. C57BL/6 J mice were used as a control group. A total of 14 differential metabolites were identified. Compared with the control group, the intensities of PI(16:0/22:5(4Z,7Z,10Z,13Z,16Z)), PC(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/18:1(9Z)), PA(16:0/18:1(11Z)), 17-beta-estradiol-3-glucuronide, and N6,N6,N6-trimethyl-L-lysine decreased significantly (p < 0.01) and the intensities of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, LysoPC(20:4(5Z,8Z,11Z,14Z)/0:0), adenosine monophosphate, adenosine-5'-phosphosulfate, LacCer(d18:1/12:0),3-dehydro-L-gulonate, N-(1-deoxy-1-fructosyl)tryptophan, homovanillic acid, and LPA(0:0/18:1(9Z)) increased significantly (p < 0.01) in the BTBR group. These changes in metabolites were closely related to perturbations in lipid metabolism, energy metabolism, purine metabolism, sulfur metabolism, amino acid metabolism, and carnitine biosynthesis. Notably, exacerbation of the oxidative stress response caused by differential prooxidant metabolites led to alteration of antioxidative systems in the cerebral cortex and resulted in mitochondrial dysfunction, further leading to abnormal energy metabolism as an etiological mechanism of autism. A central role of abnormal metabolites in neurological functions associated with behavioral outcomes and disturbance of sulfur metabolism and carnitine biosynthesis were found in the cerebral cortex of BTBR mice, which helped increase our understanding for exploring the pathological mechanism of autism.


Autistic Disorder , Mice , Animals , Mice, Inbred C57BL , Oxidative Stress , Disease Models, Animal , Cerebral Cortex , Carnitine , Sulfur
13.
Autism Res ; 15(12): 2346-2358, 2022 12.
Article En | MEDLINE | ID: mdl-36263600

Given the unpredictability and challenges brought about by the 2019 novel coronavirus (COVID-19) pandemic, this study aimed to investigate the impact trend of the prolonged pandemic on the mental health of parents of children with autism spectrum disorder (ASD). The 8112 participants included parents of children with ASD and parents of typically developing (TD) children at two sites (Heilongjiang and Fujian province, China). The parents completed a set of self-report questionnaires covering demographic characteristics, influences related to COVID-19, COVID-19 concerns and perceived behaviors, as well as the Connor-Davidson resilience scale (CD-RISC), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) by means of an online survey platform. Data were collected by three cross-sectional surveys carried out in April 2020 (Time 1), October 2020 (Time 2), and October 2021 (Time 3). The results of quantitative and qualitative comparisons showed that: (i) parents of children with ASD had lower levels of resilience, and more symptoms of anxiety and depression than parents of TD children at each time point (all P < 0.05); and (ii) there were significant time-cumulative changes in resilience, anxiety, and depression among all participants (all P < 0.05). The logistic regression analyzes after adjusting for demographic characteristics revealed that the following factors were significantly associated with poor resilience and a higher rate of anxiety and depression in parents of children with ASD: time-point, the effect of COVID-19 on children's emotions and parents' emotions, changes in relationships, changes in physical exercise, changes in daily diet during the COVID-19 pandemic, and COVID-19-related psychological distress. In conclusions, the parents did not report improvements in resilience, anxiety, or depression symptoms from Time 1 to Time 2 or 3, indicating that cumulative mental health issues increased when, surprisingly, the COVID-19 restrictions were eased. The psychological harm resulting from the COVID-19 pandemic is far-reaching, especially among parents of children with ASD.


Autism Spectrum Disorder , COVID-19 , Child , Humans , Pandemics , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/psychology , Mental Health , Cross-Sectional Studies , Parents/psychology , Anxiety/epidemiology
14.
J Hematol Oncol ; 15(1): 148, 2022 10 18.
Article En | MEDLINE | ID: mdl-36258250

Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1-2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL.Trial registration: chictr.org.cn number, ChiCTR1900023309.


Arsenic , Arsenicals , Leukemia, Promyelocytic, Acute , Humans , Adult , Leukemia, Promyelocytic, Acute/drug therapy , Tretinoin/therapeutic use , Arsenic Trioxide/therapeutic use , Arsenic Trioxide/adverse effects , Arsenic/therapeutic use , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Oxides/therapeutic use , Arsenicals/adverse effects
15.
Front Oncol ; 12: 940428, 2022.
Article En | MEDLINE | ID: mdl-36046042

Background: Perioperative anemia and transfusion are intertwined with each other, and both have adverse impacts on the survival of colorectal cancer (CRC) patients. But the treatment of anemia still relies on transfusion in several countries, which leads us to question the effects of anemia tolerance and transfusion on the long-term outcomes of CRC patients. We investigated the combined effect of preoperative anemia and postoperative anemia and of preoperative anemia and blood transfusion, which imposes a greater risk to survival, to compare the effects of anemia tolerance and transfusion on overall survival (OS) and disease-free survival (DFS) in patients undergoing CRC surgery. Methods: A retrospective propensity-score-matched analysis included patients with CRC undergoing elective surgery between January 1, 2008, and December 31, 2014. After propensity-score matching, Kaplan-Meier survival analysis and univariable and multivariable Cox proportional hazards models were used to study the prognostic factors for survivals. In univariate and multivariate Cox regression analysis, two novel models were built. Results: Of the 8,121 patients with CRC, 1,975 (24.3%) and 6,146 (75.7%) patients presented with and without preoperative anemia, respectively. After matching, 1,690 patients remained in each group. In the preoperative anemia and postoperative anemia model, preoperative anemia and postoperative anemia was independent risk factor for OS (HR, 1.202; 95% CI, 1.043-1.385; P=0.011) and DFS (HR, 1.210; 95% CI, 1.050-1.395; P=0.008). In the preoperative anemia and transfusion model, preoperative anemia and transfused was the most dangerous independent prognostic factor for OS (HR, 1.791; 95% CI, 1.339-2.397; P<0.001) and DFS (HR, 1.857; 95% CI, 1.389-2.483; P<0.001). In patients with preoperative anemia, the OS and DFS of patients with transfusion were worse than those of patients without transfusion (P=0.026 in OS; P=0.037 in DFS). Conclusions: Preoperative anemia and blood transfusion imposed a greater risk to OS and DFS in patients undergoing CRC surgery, indicating that the harm associated with blood transfusion was greater than that associated with postoperative anemia. These findings should encourage clinicians to be vigilant for the timely prevention and treatment of anemia, by appropriately promoting toleration of anemia and restricting the use of blood transfusion in patients with CRC.

16.
Front Immunol ; 13: 950782, 2022.
Article En | MEDLINE | ID: mdl-36081499

Colorectal cancer (CRC) is one of the most fatal cancers of the digestive system. Although cancer stem cells and metabolic reprogramming have an important effect on tumor progression and drug resistance, their combined effect on CRC prognosis remains unclear. Therefore, we generated a 21-gene mRNA stemness index-related metabolic risk score model, which was examined in The Cancer Genome Atlas and Gene Expression Omnibus databases (1323 patients) and validated using the Zhongshan Hospital cohort (200 patients). The high-risk group showed more immune infiltrations; higher levels of immunosuppressive checkpoints, such as CD274, tumor mutation burden, and resistance to chemotherapeutics; potentially better response to immune therapy; worse prognosis; and advanced stage of tumor node metastasis than the low-risk group. The combination of risk score and clinical characteristics was effective in predicting overall survival. Zhongshan cohort validated that high-risk score group correlated with malignant progression, worse prognosis, inferior adjuvant chemotherapy responsiveness of CRC, and shaped an immunoevasive contexture. This tool may provide a more accurate risk stratification in CRC and screening of patients with CRC responsive to immunotherapy.


Colorectal Neoplasms , Machine Learning , Chemotherapy, Adjuvant , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Humans , Prognosis , Risk Factors
17.
Front Oncol ; 12: 940706, 2022.
Article En | MEDLINE | ID: mdl-35912260

Background: Myeloperoxidase (MPO) has been demonstrated to be a local mediator of inflammation in tissue damage in various inflammatory diseases. Given its controversial effect on colorectal cancer (CRC), there has been growing interest in investigating the role of this enzyme in CRC. The mechanism underlying MPO activity and CRC progression requires further clarification. Methods: The expression and function of MPO in CRC were evaluated using TCGA analysis. TCGA, TIMER, and Human Cell Landscape analyses were used to analyze the correlation between MPO expression and neutrophil infiltration in CRC. Spearman's bivariate correlation analysis was used to verify the correlation between MPO levels in CRC and the peripheral neutrophil count. In the clinical analysis, 8,121 patients who underwent elective surgery for CRC were enrolled in this retrospective cohort study from January 2008 to December 2014. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan-Meier method and Cox regression analysis were used to identify independent prognostic factors in patients with CRC. Results: MPO was upregulated in CRC tissues, which is related to malignant progression and worse survival in CRC patients from TCGA analysis. MPO was significantly correlated with the infiltration level of neutrophils in CRC in TCGA, TIMER, and Human Cell Landscape analyses. MPO was positively correlated with the peripheral neutrophil count. Data of the 8,121 patients who underwent CRC surgery were available for analysis. After propensity score matching, 3,358 patients were included in each group. Kaplan-Meier survival curves showed that high preoperative neutrophil levels were associated with decreased overall survival (OS; P < 0.001) and disease-free survival (DFS; P = 0.015). The preoperative neutrophil count was an independent risk factor for OS (hazard ratio [HR], 1.157; 95% confidence interval [CI], 1.055-1.268; P = 0.002) and DFS (HR, 1.118; 95% CI, 1.009-1.238; P = 0.033). Conclusions: Our research indicates that increased MPO levels in CRC are significantly correlated with high preoperative neutrophil counts, and both serve as prognostic indicators for worse survival in CRC patients. Our study suggests that neutrophils may be key players in the mechanism linking MPO levels with poor CRC outcomes.

18.
Front Oncol ; 12: 927262, 2022.
Article En | MEDLINE | ID: mdl-35875149

Background: Opioids are widely used during primary debulking surgery (PDS) for ovarian cancers, and a high mu-opioid receptor (MOR) expression predicts worse cancer outcomes. However, the impact of MOR expression on survival outcomes in ovarian cancers is still not clear. Methods: A retrospective cohort study was conducted in patients who underwent PDS in ovarian cancer patients. MOR expression was measured in tumor and normal tissue. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Secondary outcomes included perineural invasion (PNI), intraoperative sufentanil consumption, length of stay (LOS), and verbal numerical rating scale (VNRS) on postoperative day 1 (POD1), POD3, and POD5. Results: After propensity score matching, a total of 366 patients were finally enrolled in this study. There were no significant differences in OS rates in patients with high versus low levels of MOR (1-year OS: 82.9% versus 83.3%, 3-year: 57.8% versus 59.1%, 5-year: 22.4% versus 23.1%,respectively) in the ovarian cancers. There were no significant differences in DFS between the groups. Intraoperative sufentanil consumption was higher in the MOR high-expression group compared with the MOR low-expression group. Tumors expressing high levels of MOR showed higher rates of PNI. VNRS in the MOR high-expression group was higher on POD1. Conclusion: MOR is not an independent predictor of worse survival in ovarian cancers but is associated with high rates of perineural invasion.

19.
J Integr Neurosci ; 21(2): 55, 2022 Mar 22.
Article En | MEDLINE | ID: mdl-35364643

BACKGROUND: Recent studies have shown that the prognosis of low-grade glioma (LGG) patients is closely correlated with the immune infiltration and the expression of long-stranded non-coding RNAs (lncRNAs). It's meaningful to find the immune-related lncRNAs (irlncRNAs). METHODS: The Cancer Genome Atlas (TCGA) data was employed in the study to identify irlncRNAs and Cox regression model was applied to construct the risk proportional model based on irlncRNAs. RESULTS: In the study, we retrieved transcriptomic data of LGG from TCGA and identified 10 lncRNA signatures consisting of irlncRNAs by co-expression analysis. Then we plotted 1-year receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC). LGG patients were divided into high-risk and low-risk groups according to the risk model. We found there were differences in survival prognosis, clinical characteristics, degree of immune cell infiltration, expression of immune gene checkpoint genes, and sensitivity to the commonly used chemotherapeutic agents of high-risk and low-risk groups. CONCLUSIONS: IrlncRNA-based risk assessment model can be used as a prognostic tool to predict the survival outcome and clinical characteristics of LGG and to guide treatment options.


Glioma , RNA, Long Noncoding , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Glioma/genetics , Glioma/therapy , Humans , Prognosis , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
20.
Acta Neurochir (Wien) ; 164(3): 689-702, 2022 03.
Article En | MEDLINE | ID: mdl-34636967

PURPOSE: To compare the multimodal techniques (including neuronavigation, intraoperative MRI [iMRI], and neuromonitoring [IONM]) and conventional approach (only guided by neuronavigation) in removing glioblastoma (GBM) with corpus callosum (CC) involvement (ccGBM), their effectiveness and safety were analyzed and compared. METHODS: Electronic medical records were retrospectively reviewed for ccGBM cases treated in our hospital between January 2016 and July 2020. Patient demographics, tumor characteristics, clinical outcomes, extent of resection (EOR), progression-free survival (PFS), and overall survival (OS) were obtained and compared between the multimodal group (used multimodal techniques) and the conventional group (only used neuronavigation). Both groups only included patients that had maximal safe resection (not biopsy). Postoperative radiochemotherapy was also performed or not. Univariate and multivariate analyses were performed to identify significant prognostic factors and optimal EOR threshold. RESULTS: Finally 56 cases of the multimodal group and 21 cases of the conventional group were included. The multimodal group achieved a higher median EOR (100% versus 96.1%, P = 0.036) and gross total resection rate (60.7% versus 33.3%, P = 0.032) and a lower rate of permanent motor deficits (5.4% versus 23.8%, P = 0.052) than the conventional approach. The multimodal group had the longer median PFS (10.9 versus 7.0 months, P = 0.023) and OS (16.1 versus 11.6 months, P = 0.044) than the conventional group. Postoperative language and cognitive function were similar between the two groups. In multivariate analysis, a higher EOR, radiotherapy, and longer cycles of temozolomide chemotherapy were positive prognostic factors for survival of ccGBM. An optimal EOR threshold of 92% was found to significantly benefit the PFS (HR = 0.51, P = 0.036) and OS (HR = 0.49, P = 0.025) of ccGBM. CONCLUSION: Combined use of multimodal techniques can optimize the safe removal of ccGBM. Aggressive resection of EOR > 92% using multimodal techniques combined with postoperative radiochemotherapy should be suggested for ccGBM.


Brain Neoplasms , Glioblastoma , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Corpus Callosum/diagnostic imaging , Corpus Callosum/pathology , Corpus Callosum/surgery , Glioblastoma/diagnostic imaging , Glioblastoma/surgery , Humans , Magnetic Resonance Imaging/methods , Monitoring, Intraoperative/methods , Neurosurgical Procedures/methods , Retrospective Studies , Treatment Outcome
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